Dataset Information

Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants.

ABSTRACT: Exploring linkage disequilibrium (LD) patterns among the single nucleotide polymorphism (SNP) sites can improve the accuracy and cost-effectiveness of genomic association studies, whereby representative (tag) SNPs are identified to sufficiently represent the genomic diversity in populations. There has been considerable amount of effort in developing efficient algorithms to select tag SNPs from the growing large-scale data sets. Methods using the classical pairwise-LD and multi-locus LD measures have been proposed that aim to reduce the computational complexity and to increase the accuracy, respectively. The present work solves the tag SNP selection problem by efficiently balancing the computational complexity and accuracy, and improves the coverage in genomic diversity in a cost-effective manner. The employed algorithm makes use of mutual information to explore the multi-locus association between SNPs and can handle different data types and conditions. Experiments with benchmark HapMap data sets show comparable or better performance against the state-of-the-art algorithms. In particular, as a novel application, the genome-wide SNP tagging is performed in the 1000 Genomes Project data sets, and produced a well-annotated database of tagging variants that capture the common genotype diversity in 2,504 samples from 26 human populations. Compared to conventional methods, the algorithm requires as input only the genotype (or haplotype) sequences, can scale up to genome-wide analyses, and produces accurate solutions with more information-rich output, providing an improved platform for researchers towards the subsequent association studies.

SUBMITTER: Elmas A

PROVIDER: S-EPMC5161470 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants.

Elmas Abdulkadir A Ou Yang Tai-Hsien TH Wang Xiaodong X Anastassiou Dimitris D

PloS one 20161216 12

Exploring linkage disequilibrium (LD) patterns among the single nucleotide polymorphism (SNP) sites can improve the accuracy and cost-effectiveness of genomic association studies, whereby representative (tag) SNPs are identified to sufficiently represent the genomic diversity in populations. There has been considerable amount of effort in developing efficient algorithms to select tag SNPs from the growing large-scale data sets. Methods using the classical pairwise-LD and multi-locus LD measures ...[more]

PMID: 27992465

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Project description:BackgroundPredicting protein contacts solely based on sequence information remains a challenging problem, despite the huge amount of sequence data at our disposal. Mutual Information (MI), an information theory measure, has been extensively employed and modified to identify residues within a protein (intra-protein) that are in contact. More recently MI and its variants have also been used in the prediction of contacts between proteins (inter-protein).MethodsHere we assess the predictive power of MI and variants for domain-domain contact prediction. We test original MI and these variants, which are called MIp, MIc and ZNMI, on 40 domain-domain test cases containing 10,753 sequences. We also propose and evaluate two new versions of MI that consider triangles of residues and the physiochemical properties of the amino acids, respectively.ResultsWe found that all versions of MI are skewed towards predicting surface residues. Since domain-domain contacts are on the surface of each domain, we considered only surface residues when attempting to predict contacts. Our analysis shows that MIc is the best current MI domain-domain contact predictor. At 20% recall MIc achieved a precision of 44.9% when only surface residues were considered. Our triangle and reduced alphabet variants of MI highlight the delicate trade-off between signal and noise in the use of MI for domain-domain contact prediction. We also examine a specific "successful" case study and demonstrate that here, when considering surface residues, even the most accurate domain-domain contact predictor, MIc, performs no better than random.ConclusionsAll tested variants of MI are skewed towards predicting surface residues. When considering surface residues only, we find MIc to be the best current MI domain-domain contact predictor. Its performance, however, is not as good as a non-MI based contact predictor, i-Patch. Additionally, the intra-protein contact prediction capabilities of MIc outperform its domain-domain contact prediction abilities.

Project description:BackgroundSingle Nucleotide Polymorphisms (SNPs) are the most common type of polymorphisms found in the human genome. Effective genetic association studies require the identification of sets of tag SNPs that capture as much haplotype information as possible. Tag SNP selection is analogous to the problem of data compression in information theory. According to Shannon's framework, the optimal tag set maximizes the entropy of the tag SNPs subject to constraints on the number of SNPs. This approach requires an appropriate probabilistic model. Compared to simple measures of Linkage Disequilibrium (LD), a good model of haplotype sequences can more accurately account for LD structure. It also provides a machinery for the prediction of tagged SNPs and thereby to assess the performances of tag sets through their ability to predict larger SNP sets.ResultsHere, we compute the description code-lengths of SNP data for an array of models and we develop tag SNP selection methods based on these models and the strategy of entropy maximization. Using data sets from the HapMap and ENCODE projects, we show that the hidden Markov model introduced by Li and Stephens outperforms the other models in several aspects: description code-length of SNP data, information content of tag sets, and prediction of tagged SNPs. This is the first use of this model in the context of tag SNP selection.ConclusionOur study provides strong evidence that the tag sets selected by our best method, based on Li and Stephens model, outperform those chosen by several existing methods. The results also suggest that information content evaluated with a good model is more sensitive for assessing the quality of a tagging set than the correct prediction rate of tagged SNPs. Besides, we show that haplotype phase uncertainty has an almost negligible impact on the ability of good tag sets to predict tagged SNPs. This justifies the selection of tag SNPs on the basis of haplotype informativeness, although genotyping studies do not directly assess haplotypes. A software that implements our approach is available.

Dataset Information

Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants.

Publications

Discovering Genome-Wide Tag SNPs Based on the Mutual Information of the Variants.

Similar Datasets

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